The present invention relates to a DNA containing a DNA segment coding for a Xenopus laevis bone morphogenetic protein analogous to a bone morphogenetic protein (hereinafter referred to as BMP), a precursor protein (or a precursor polypeptide) and a mature protein (or a mature polypeptide) of the Xenopus laevis BMP, and a method for preparing the precursor protein and the mature protein.
In this specification, the term "precursor protein" includes a protein which includes an amino acid sequence of a mature peptide Xenopus Laevis BMP and has all or a portion of an amino acid sequence coded with a Xenopus laevis BMP DNA segment at the N-terminus, the C-terminus or both termini thereof.
Recently, it has been revealed that transforming growth factor-beta (TGF-beta, TGF-.beta.) having a bone morphogenetic activity not only controls cell proliferation, but also has various biological activities such as control of cell differentiation. In particular, the bone morphogenesis-promoting activity of TGF-.beta. has been noted, and attempts have been made to use TGF for treatment of fractures and osteoporosis, making use of the cartilage-bone induction activity thereof [M. Noda et al., J. Endocrinology 124, 2991-2994 (1989); M. E. Joyce et al., J. Bone Mineral Res. 4, S-259 (1989); and S. M. Seyedin et al., J. Biol. Chem. 281, 5693-5695 (1986)]. More recently, however, four kinds of bone morphogenetic proteins (BMPs) which are different from one another in molecular structure have been identified as a factor promoting morphogenesis of bones and cartilages. Of these four kinds, human BMP-1, human BMP-2A, human BMP-2B and human BMP-3 are novel peptides, though they are very similar in structure to TGF-.beta., and there has been a report that they induce morphogenesis of bones and cartilages when subcutaneously or intramuscularly implanted in animals [J. M. Wozney et al., Science 242, 1528-1534 (1989)].
The above peptides having bone morphogenetic activity are isolated and purified from bones in which the peptides are considered to be localized, or from human osteosarcoma cells (U2-OS) which are thought to produce the peptides. However, such a method has problems because the procedure is complicated and the desired peptides are obtained only in small amounts.